Changes in the transcriptional profile of transporters in the intestine along the anterior-posterior and crypt-villus axes

Pascale Anderle¹ , Thierry Sengstag² , David M Mutch³ , Martin Rumbo¹ , Viviane Praz⁴ , Robert Mansourian³ , Mauro Delorenzi² , Gary Williamson³ and Matthew-Alan Roberts⁵

¹ISREC, Swiss Institute for Experimental Cancer Research, 1066 Epalinges s/Lausanne, Switzerland

²Swiss Institute for Experimental Cancer Research (ISREC) and Swiss Institute of Bioinformatics (SIB), NCCR Molecular Oncology, CH-1066 Epalinges s/Lausanne, Switzerland

³Nestle Research Center, Vers-chez-les-Blanc, 1000 Lausanne 26, Switzerland

⁴ISREC and Swiss Institute of Bioinformatics, 1066 Epalinges s/Lausanne, Switzerland

⁵Nestle Purina Pet Care, St. Louis, Missouri 63164, USA

author email corresponding author email

BMC Genomics 2005, 6:69doi:10.1186/1471-2164-6-69


Published:	10 May 2005

Abstract

Background

The purpose of this work was to characterize the expression of drug and nutrient carriers along the anterior-posterior and crypt-villus axes of the intestinal epithelium and to study the validity of utilizing whole gut tissue rather than purified epithelial cells to examine regional variations in gene expression.

Results

We have characterized the mRNA expression profiles of 76 % of all currently known transporters along the anterior-posterior axis of the gut. This is the first study to describe the expression profiles of the majority of all known transporters in the intestine. The expression profiles of transporters, as defined according to the Gene Ontology consortium, were measured in whole tissue of the murine duodenum, jejunum, ileum and colon using high-density microarrays. For nine transporters (Abca1, Abcc1, Abcc3, Abcg8, Slc10a2, Slc28a2, Slc2a1, Slc34a2 and Slc5a8), the mRNA profiles were further measured by RT-PCR in laser micro-dissected crypt and villus epithelial cells corresponding to the aforementioned intestinal regions. With respect to differentially regulated transporters, the colon had a distinct expression profile from small intestinal segments. The majority (59 % for p cutoff ≤ 0.05) of transporter mRNA levels were constant across the intestinal sections studied. For the transporter subclass "carrier activity", which contains the majority of known carriers for biologically active compounds, a significant change (p ≤ 0.05) along the anterior-posterior axis was observed.

Conclusion

All nine transporters examined in laser-dissected material demonstrated good replication of the region-specific profiles revealed by microarray. Furthermore, we suggest that the distribution characteristics of Slc5a8 along the intestinal tract render it a suitable candidate carrier for monocarboxylate drugs in the posterior portion of the intestine. Our findings also predict that there is a significant difference in the absorption of carrier-mediated compounds in the different intestinal segments. The most pronounced differences can be expected between the adjoining segments ileum and colon, but the differences between the other adjoining segments are not negligible. Finally, for the examined genes, profiles measured in whole intestinal tissue extracts are representative of epithelial cell-only gene expression.